Parameter Orthogonality in Mixed Regression Models for Survival Data

The implications of parameter orthogonality for the robustness of survival regression models are considered. The question of which of the proportional hazards or the accelerated life families of models would be more appropriate for analysis is usually ignored, and the proportional hazards family is applied, particularly in medicine, for convenience. Accelerated life models have conventionally been used in reliability applications. We propose a one-parameter family mixture survival model which includes both the accelerated life and the proportional hazards models. By orthogonalizing relative to the mixture parameter, we can show that, for small effects of the covariates, the regression parameters under the alternative families agree to within a constant. This recovers a known misspecification result. We use notions of parameter orthogonality to explore robustness to other types of misspecification including misspecified base-line hazards. The results hold in the presence of censoring. We also study the important question of when proportionality matters.     

Shared frailty model based on reversed hazard rate for left censored data

Frailty models are used in the survival analysis to account for the unobserved heterogeneity in the individual risks to disease and death. To analyze the bivariate data on related survival times (e.g., matched pairs experiments, twin or family data), the shared frailty models were suggested. In this article, we introduce the shared gamma frailty models with the reversed hazard rate. We develop the Bayesian estimation procedure using the Markov chain Monte Carlo (MCMC) technique to estimate the parameters involved in the model. We present a simulation study to compare the true values of the parameters with the estimated values. We apply the model to a real life bivariate survival dataset.     

Correlated gamma frailty models for bivariate survival data

Frailty models are used in the survival analysis to account for the unobserved heterogeneity in individual risks to disease and death. To analyze the bivariate data on related survival times (e.g., matched pairs experiments, twin or family data) the shared frailty models were suggested. Shared frailty models are used despite their limitations. To overcome their disadvantages correlated frailty models may be used. In this article, we introduce the gamma correlated frailty models with two different baseline distributions namely, the generalized log logistic, and the generalized Weibull. We introduce the Bayesian estimation procedure using Markov chain Monte Carlo (MCMC) technique to estimate the parameters involved in these models. We present a simulation study to compare the true values of the parameters with the estimated values. Also we apply these models to a real life bivariate survival dataset related to the kidney infection data and a better model is suggested for the data.     

Joint analysis of longitudinal measurements and survival times with a cure fraction based on partly linear mixed and semiparametric cure models

In a joint analysis of longitudinal quality of life (QoL) scores and relapse-free survival (RFS) times from a clinical trial on early breast cancer conducted by the Canadian Cancer Trials Group, we observed a complicated trajectory of QoL scores and existence of long-term survivors. Motivated by this observation, we proposed in this paper a flexible joint model for the longitudinal measurements and survival times. A partly linear mixed effect model is used to capture the complicated but smooth trajectory of longitudinal measurements and approximated by B-splines and a semiparametric mixture cure model with the B-spline baseline hazard to model survival times with a cure fraction. These two models are linked by shared random effects to explore the dependence between longitudinal measurements and survival times. A semiparametric inference procedure with an EM algorithm is proposed to estimate the parameters in the joint model. The performance of proposed procedures are evaluated by simulation studies and through the application to the analysis of data from the clinical trial which motivated this research.     

Some results on discrete mixture failure rates

Some properties of the discrete mixture failure rates are studied. Specifically, similar to the continuous case, it is shown that the population mixture failure rate is always smaller than the unconditional expectation in the family of subpopulations failure rates. The analog of the multiplicative and the additive frailty models is introduced via the corresponding survival function. Another approach via the alternative discrete failure rate is also discussed. Stochastic comparisons for two mixed distributions with equal and different mixing distributions are studied.     

Estimating the cure fraction in population-based cancer studies by using finite mixture models

Summary.  The cure fraction (the proportion of patients who are cured of disease) is of interest to both patients and clinicians and is a useful measure to monitor trends in survival of curable disease. The paper extends the non-mixture and mixture cure fraction models to estimate the proportion cured of disease in population-based cancer studies by incorporating a finite mixture of two Weibull distributions to provide more flexibility in the shape of the estimated relative survival or excess mortality functions. The methods are illustrated by using public use data from England and Wales on survival following diagnosis of cancer of the colon where interest lies in differences between age and deprivation groups. We show that the finite mixture approach leads to improved model fit and estimates of the cure fraction that are closer to the empirical estimates. This is particularly so in the oldest age group where the cure fraction is notably lower. The cure fraction is broadly similar in each deprivation group, but the median survival of the 'uncured' is lower in the more deprived groups. The finite mixture approach overcomes some of the limitations of the more simplistic cure models and has the potential to model the complex excess hazard functions that are seen in real data.     

Covariate effect on the life expectancy and percentile residual life functions under the proportional hazards and the accelerated life models

The present paper is concerned with statistical models for the dependence of survival time or time to occurrence of an event, such as time to tumor, on a vector X of covariates or prognostic variables such as age, sex, blood pressure, length of exposure to a toxic material, etc., measured on a group of individuals in biomedical investigations. It is assumed that the covariates influence the distribution of time to tumor only through a linear predictor μ =β^′X.

The object of our paper is to investigate the effect due to the covariates on the Life Expectancy and the Percentile Residual Life (PRL) function of a family of organisms under the proportional hazards and the accelerated life models. The key result is that the families of survival distributions under these models have the 'setting the clock back to zero' property if the family of baseline survival distributions does. This property is a generalization of the lack of memory property of the exponential distribution. Simple examples of the members of this family are the linear hazard exponential, Pareto and Gompertz life distributions.

As a simple application of the main results obtained in the present paper, we have considered a stochastic survival model recently proposed by Chiang and Conforti (1989) for the time-to-tumor distribution in the context of a large-scale serial sacrifice experiment by the National Center of Toxicological Research (NCTR). This involves some mice that were fed 2-AAF from infancy and those that developed bladder and/or liver neoplasms, see Farmer et al (1980). It is shown that their stochastic model for tumor incidence intensity at time t leads to a family of survival models that has the setting the clock back to zero property. The survival functions and the effect of the vector X of covariates on the PRL and the tumor-free life expectancies are evaluated for the proportional hazards and accelerated life models.     

Product-limit survival functions with correlated survival times

A simple variance estimator for product-limit survival functions is demonstrated for survival times with nested errors. Such data arise whenever survival times are observed within clusters of related observations. Greenwood's formula, which assumes independent observations, is not appropriate in this situation. A robust variance estimator is developed using Taylor series linearized values and the between-cluster variance estimator commonly used in multi-stage sample surveys. A simulation study shows that the between-cluster variance estimator is approximately unbiased and yields confidence intervals that maintain the nominal level for several patterns of correlated survival times. The simulation study also shows that Greenwood's formula underestimates the variance when the survival times are positively correlated within a cluster and yields confidence intervals that are too narrow. Extension to life table methods is also discussed.     

The Gini concentration test for survival data

We apply the well known Gini index to the measurement of concentration in survival times within groups of patients, and as a way to compare the distribution of survival times across groups of patients in clinical studies. In particular, we propose an estimator of a restricted version of the index from right censored data. We derive the asymptotic distribution of the resulting Gini statistic, and construct an estimator for its asymptotic variance. We use these results to propose a novel test for differences in the heterogeneity of survival distributions, which may suggest the presence of a differential treatment effect for some groups of patients. We focus in particular on traditional and generalized cure rate models, i.e., mixture models with a distribution of the lifetimes of the cured patients that is either degenerate at infinity or has a density. Results from a simulation study suggest that the Gini index is useful in some situations, and that it should be considered together with existing tests (in particular, the Log-rank, Wilcoxon, and Gray–Tsiatis tests). Use of the test is illustrated on the classic data arising from the Eastern Cooperative Oncology Group melanoma clinical trial E1690.     

A Comparison of Two Alternative Approaches to Modeling Level Shifts in the Presence of Outliers

Abstract

We study alternative models for capturing abrupt structural changes (level shifts) in a times series. The problem is confounded by the presence of transient outliers. We compare the performance of non-Gaussian time-varying parameter models and multiprocess mixture models within a Monte Carlo experimental setup. Our findings suggest that once we incorporate shocks with thick-tailed probability distributions, the superiority of the multiprocess mixture models over the time-varying parameter models, reported in an earlier study, disappears. The behavior of the two models, both in adapting to level shifts and in reacting to transient outliers, is very similar.     

Profile likelihood approaches for semiparametric copula and frailty models for clustered survival data

ABSTRACT

In clustered survival data, the dependence among individual survival times within a cluster has usually been described using copula models and frailty models. In this paper we propose a profile likelihood approach for semiparametric copula models with different cluster sizes. We also propose a likelihood ratio method based on profile likelihood for testing the absence of association parameter (i.e. test of independence) under the copula models, leading to the boundary problem of the parameter space. For this purpose, we show via simulation study that the proposed likelihood ratio method using an asymptotic chi-square mixture distribution performs well as sample size increases. We compare the behaviors of the two models using the profile likelihood approach under a semiparametric setting. The proposed method is demonstrated using two well-known data sets.     

Gamma failure‐time mixture models: yet another way to establish efficacy

Using a Yamaguchi‐type generalized gamma failure‐time mixture model, we analyse the data from a study of autologous and allogeneic bone marrow transplantation in the treatment of high‐risk refractory acute lymphoblastic leukaemia, focusing on the time to recurrence of disease. We develop maximum likelihood techniques for the joint estimation of the surviving fractions and the survivor functions. This includes an approximation to the derivative of the survivor function with respect to the shape parameter. We obtain the maximum likelihood estimates of the model parameters. We also compute the variance‐covariance matrix of the parameter estimators. The extended family of generalized gamma failure‐time mixture models is flexible enough to include many commonly used failure‐time distributions as special cases. Yet these models are not used in practice because of computational difficulties. We claim that we have overcome this problem. The proposed approximation to the derivative of the survivor function with respect to the shape parameter can be used in any statistical package. We also address the issue of lack of identifiability. We point out that there can be a substantial advantage to using the gamma failure‐time mixture models over nonparametric methods. Copyright © 2003 John Wiley & Sons, Ltd.     

Extending mixtures of multivariate <Emphasis Type="Italic">t</Emphasis>-factor analyzers

Model-based clustering typically involves the development of a family of mixture models and the imposition of these models upon data. The best member of the family is then chosen using some criterion and the associated parameter estimates lead to predicted group memberships, or clusterings. This paper describes the extension of the mixtures of multivariate t-factor analyzers model to include constraints on the degrees of freedom, the factor loadings, and the error variance matrices. The result is a family of six mixture models, including parsimonious models. Parameter estimates for this family of models are derived using an alternating expectation-conditional maximization algorithm and convergence is determined based on Aitken’s acceleration. Model selection is carried out using the Bayesian information criterion (BIC) and the integrated completed likelihood (ICL). This novel family of mixture models is then applied to simulated and real data where clustering performance meets or exceeds that of established model-based clustering methods. The simulation studies include a comparison of the BIC and the ICL as model selection techniques for this novel family of models. Application to simulated data with larger dimensionality is also explored.     

Distribution of the random future life expectancies in log-bilinear mortality projection models

Projected life tables are obtained from forecasting methods and account for future improvements in longevity. Since the future path of mortality is unknown, working with projected life tables makes the survival probabilities stochastic. The resulting demographic indicators in turn become random variables. This paper aims to study the distribution of period and cohort life expectancies derived from projected life tables. To fix the ideas, we adopt here the standard Lee–Carter framework, where the future forces of mortality are decomposed in a log-bilinear way. Exact formulas are derived for period life expectancies, and approximations are proposed for cohort life expectancies. In the latter case, numerical illustrations based on Belgian population data show that the relative accuracy is remarkable.     

Mixture modelling of recurrent event times with long-term survivors: Analysis of Hutterite birth intervals

We propose a mixture model that combines a discrete-time survival model for analyzing the correlated times between recurrent events, e.g. births, with a logistic regression model for the probability of never experiencing the event of interest, i.e., being a long-term survivor. The proposed survival model incorporates both observed and unobserved heterogeneity in the probability of experiencing the event of interest. We use Gibbs sampling for the fitting of such mixture models, which leads to a computationally intensive solution to the problem of fitting survival models for multiple event time data with long-term survivors. We illustrate our Bayesian approach through an analysis of Hutterite birth histories.     

On the generalized process capability under simple and mixture models

Process capability (PC) indices measure the ability of a process of interest to meet the desired specifications under certain restrictions. There are a variety of capability indices available in literature for different interest variables such as weights, lengths, thickness, and the life time of items among many others. The goal of this article is to study the generalized capability indices from the Bayesian view point under different symmetric and asymmetric loss functions for the simple and mixture of generalized lifetime models. For our study purposes, we have covered a simple and two component mixture of Maxwell distribution as a special case of the generalized class of models. A comparative discussion of the PC with the mixture models under Laplace and inverse Rayleigh are also included. Bayesian point estimation of maintenance performance of the system is also part of the study (considering the Maxwell failure lifetime model and the repair time model). A real-life example is also included to illustrate the procedural details of the proposed method.     

Frailty regression models in mixture distributions

We propose frailty regression models in mixture distributions and assume the distribution of frailty as gamma or positive stable or power variance function distribution. We consider Weibull mixture as an example. There are some interesting situations like survival times in genetic epidemiology, dental implants of patients and twin births (both monozygotic and dizygotic) where genetic behavior (which is unknown and random) of patients follows a known frailty distribution. These are the situations which motivate to study this particular model.     

Statistical Analysis of General Degradation Path Model and Failure Time Data with Multiple Failure Modes

ABSTRACT

This article considers degradation and failure time models with multiple failure modes which used to study the problem of longevity and aging in survival analysis and reliability. Degradation process is modeled using general nonparametric, nonlinear path models. Semi-parametric models for the intensities of the traumatic failures are used supposing that these intensities depend on degradation level. Semi-parametric estimators of various reliability characteristics are proposed and asymptotic properties of the estimators are obtained. The theoretical results are illustrated using simulated data.     

Bayesian Semiparametric Regression for Median Residual Life

Abstract.  With survival data there is often interest not only in the survival time distribution but also in the residual survival time distribution. In fact, regression models to explain residual survival time might be desired. Building upon recent work of Kottas & Gelfand [ J. Amer. Statist. Assoc. 96 (2001) 1458], we formulate a semiparametric median residual life regression model induced by a semiparametric accelerated failure time regression model. We utilize a Bayesian approach which allows full and exact inference. Classical work essentially ignores covariates and is either based upon parametric assumptions or is limited to asymptotic inference in non-parametric settings. No regression modelling of median residual life appears to exist. The Bayesian modelling is developed through Dirichlet process mixing. The models are fitted using Gibbs sampling. Residual life inference is implemented extending the approach of Gelfand & Kottas [ J. Comput. Graph. Statist. 11 (2002) 289]. Finally, we present a fairly detailed analysis of a set of survival times with moderate censoring for patients with small cell lung cancer.     

A Comparison of Methods for Analysing a Nested Frailty Model to Child Survival in Malawi

Demographic and Health Surveys collect child survival times that are clustered at the family and community levels. It is assumed that each cluster has a specific, unobservable, random frailty that induces an association in the survival times within the cluster. The Cox proportional hazards model, with family and community random frailties acting multiplicatively on the hazard rate, is presented. The estimation of the fixed effect and the association parameters of the modified model is then examined using the Gibbs sampler and the expectation–maximization (EM) algorithm. The methods are compared using child survival data collected in the 1992 Demographic and Health Survey of Malawi. The two methods lead to very similar estimates of fixed effect parameters. However, the estimates of random effect variances from the EM algorithm are smaller than those of the Gibbs sampler. Both estimation methods reveal considerable family variation in the survival of children, and very little variability over the communities.